Frequently, the therapeutic efficacy of a promising pharmaceutical agent is undermined as a result of one or more unfavorable pharmacokinetic properties exhibited by the agent when it is administered in vivo to a patient. Indeed, achieving an optimum balance between a drug's various pharmacokinetic properties remains a significant challenge within the pharmaceutical field.
By way of example, the absorption kinetics of a drug (e.g., the degree to which and the duration of time over which a drug is absorbed by a patient), the inter- and intra-subject variability of a drug's absorption, the plasma concentration of a drug and its steadiness over time, the occurrence of dangerous concentration surges in a drug's maximum concentration (Cmax), the general bioavailability of a drug, the toxicity of a drug, and the like are all factors in determining the therapeutic utility and efficacy of prospective drug candidates. If an acceptable balance in these and other parameters cannot be achieved and/or if the cost/benefit ratio associated with the drug's use is deemed inadequate, a drug candidate may be discarded regardless of its promise in treating a particular malady.
Unfavorable pharmacokinetic properties can also limit the use, safety or effectiveness of marketed drugs. Representative drugs that—notwithstanding their established or presumptive efficacies in treating certain disorders—are deemed to be lacking with respect to one or more of their pharmacokinetic properties include but are not limited to levodopa (LD) in the treatment of Parkinson's disease (PD), 3,5,3′-triiodothyronine (T3) in the treatment of hypothyroidism, mesalamine in the treatment of ulcerative colitis (UC), and dichloroacetate (DCA) in the treatment of cancer.
In short, the ability to modulate a pharmacokinetic property of a biologically active agent (e.g., to provide extended release, improved bioavailability, enhanced absorption, reduced variability, an extended therapeutic window, safe plasma levels, and the like) would be highly desirable.